Pediatric Myelodysplastic Syndrome Treatment & Management

Updated: Jun 03, 2022
  • Author: Meena Kadapakkam, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
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Approach Considerations

Administer supportive care until the diagnosis is established. Many patients present with profound cytopenia and a notable risk for infection. Transfusions and broad-spectrum antibiotics may be required to treat life-threatening anemia, thrombocytopenia, and infection until definitive therapy can be started.

In patients with refractory cytopenia, hematopoietic stem cell transplantation (HSCT) from a matched related or well-matched unrelated donor early in the course of the disease is the treatment of choice, especially in those with monosomy 7, 7q-, or complex karyotype. Family members of children with monosomy 7 cytogenetics should be evaluated for familial monosomy 7.

Children with refractory cytopenia and a normal karyotype or chromosomal abnormalities other than aberrations of chromosome 7 and absence of transfusion dependency or severe neutropenia may be carefully observed over time. If the cytopenias necessitate treatment, then options include HSCT with either myeloablative or reduced intensity preparative therapies.

HSCT is also indicated for patients with increasing blast counts concerning for malignant transformation, especially in those with GATA2 mutations. 

Treatment with hematopoietic growth factors may be indicated.

Splenectomy may prove helpful in patients with marked splenomegaly or hypersplenia. The great risk is infection, as is the case with any patient who is asplenic. No significant change in the event-free survival rate is noted in splenectomized patients who undergo hematopoietic stem cell rescue.

Some patients may respond to immunosuppressive therapy with cyclosporine and antithymocyte globulin. Yoshimi et al reported a pilot study involving 29 children who received therapy with these agents. [24] At 6 months, 22 children had a complete or partial response. Six patients were subsequently transplanted for nonresponse, progression, or evolution of monosomy 7. Overall and failure-free survivals were 89% and 55%, respectively.

No dietary restrictions are needed. Patients should take adequate amounts of folate and vitamin B-12. Limitation of iron intake may be necessary in patients who are transfusion dependent. Activity should be undertaken as tolerated. Restriction of activity when platelet counts are low is necessary to prevent hemorrhagic complications from minor trauma.

Consultation may be indicated with a pediatric hematologist/oncologist. A clinical geneticist may provide an invaluable opinion for many children because of the notable association of MSD with other anomalies. Patients should be referred to centers affiliated with major multicenter pediatric oncologic groups.

Children should be monitored often because of the propensity of these disorders to transform to AML. Patients often require frequent transfusions, and their blood cell counts must be monitored at least monthly. Repeated transfusions may result in iron overload, requiring chelation therapy. However, iron overload is observed most often in adults with MDS related to transfusions over a prolonged course.

Patients who have undergone myeloablative therapy with stem cell rescue should be monitored for long-term sequelae, including short stature, obesity, gonadal failure, hypothyroidism, and cataracts.


Hematopoietic Stem Cell Transplantation

Because MDS is a clonal early stem-cell disorder with very limited residual nonclonal stem cells, myeloablative therapy is the only treatment option with a realistic curative potential. Regimens for hematopoietic stem cell rescue result in a 30-50% event-free survival (EFS) rate at 3 years. Outcomes improve in children who are relatively young and who receive hematopoietic stem cell rescue soon after diagnosis.

Myeloablative therapy with hematopoietic stem cell rescue from a human leukocyte antigen (HLA)–matched sibling is the best therapy for MDS. For children who do not have an eligible sibling donor, alternative donors should be sought, although outcome is even less favorable than it is with a sibling donor. A study by Lang et al reported 5-year EFS rates of 60% and 47% for HSCT using matched sibling donors or compatible unrelated donors, respectively. [25]

In a cohort of 27 children with refractory cytopenia, Yusuf et al reported an estimated survival probability of 0.74 following various high-intensity conditioning regimens. [26] In an Italian study involving 49 children, using the busulfan/cyclophosphamide regimen, the 5-year estimate of EFS rate was 77%, whereas the 5-year cumulative incidence of transplantation-related mortality and disease recurrence were 19% and 2%, respectively.

A cohort of 16 children, 14 of whom met the criteria for MDS, received allogeneic stem cell transplants. Median age was 4.8 years (range 1-14 y). The median time from diagnosis to transplant was 6 months. Eleven of 14 patients were conditioned with a busulphan-based myeloablative regimen, with the addition of low-dose etoposide, and all but one received a bone marrow graft. Nine patients achieved complete remission. At a median follow-up of 3 years (range 2-14 y), the overall survival and EFS was 57% (95% confidence interval, 0.28-0.78). Cumulative EFS at 10 y was 43% (95% confidence interval, 0.14-0.70). Relapse-related mortality was 21.4%. [27]

In a single-center experience with 37 consecutive pediatric MDS patients (20 had primary MDS, and 17 had secondary MDS) who received myeloablative HSCT (majority received cyclophosphamide/total body irradiation conditioning regimen),the overall survival and disease-free survival at 10 years was 53% and 45%, respectively. Monosomy 7 was present in 21, trisomy 8 in 7, and normal cytogenetics in 8. According to the modified WHO criteria, 30 had RC and 7 had RAEB. The 3-year disease-free survival in patients who did not receive pre-HSCT chemotherapy and those who had a shorter interval to transplantation (< 140 d) was 80%. [28]

These data indicate that transplant-related mortality represents the main cause of treatment failure. Using a reduced-intensity conditioning regimen with fludarabine, Strahm et al reported that in 19 children with refractory cytopenia, the 3-year overall survival and EFS were 0.84 and 0.74, respectively. [29]

In patients with myelodysplastic syndrome (MDS) who have an increased blast count, allogeneic HSCT is the treatment of choice. Toxicity of the procedure and relapse rate contribute equally to the number of adverse events.

Whether intensive chemotherapy should be routinely administered prior to HSCT is highly controversial. In the United States and United Kingdom, children with refractory anemia with excess blasts (RAEB) and RAEB in transition to acute myeloid leukemia (AML) are generally included in pediatric AML trials.

Most AML studies have reported significant morbidity and mortality in patients with MDS, and an overall survival of less than 30%. [30, 31] Zecca et al reported that AML-type therapy prior to HSCT did not prolong survival in 101 children with MDS and an increased blast count.


Agents Used in Adults

The US Food and Drug Administration (FDA) has approved three agents for treatment of adult MDS since 2004: azacitidine (Vidaza), decitabine (Dacogen) and lenalidomide (Revlimid). Decitabine and lenalidomide have not been approved for the pediatric population. Studies should be undertaken to elucidate the efficacy of these agents in the pediatric population; however, pediatric MDS does not seen to have driver epigenetic mutations unlike adult MDS. In 2022, the FDA approved azacitidine for pediatric patients with newly diagnosed juvenile myelomonocytic leukemia.

In adults, lenalidomide is approved for the treatment of transfusion-dependent anemia in patients with MDS and chromosome 5q deletion. In the pivotal trial, 76% of patients had a 50% or greater reduction in transfusions, with 67% achieving transfusion independence. [32] Achievement of transfusion independence strictly correlated with cytogenetic response. In addition, cytogenetic response had the highest predictive value for prolonged survival in a multivariate analysis, as well as a statistically significant decreased risk for AML progression.

Azacitidine and decitabine have become established as part of the standard medications in the treatment of MDS in adults. In a phase III study of azacitidine, Silverman et al reported an overall response rate of 60% in 191 patients, with 7% complete response, 16% partial response, and 37% hematological response. [33] In a phase III study using decitabine, Kantarian et al reported an overall response rate of 17% in 170 patients, with 9% complete response, 8% partial response, and 13% hematologic response. [34]

Data from a study by Bernal et al showed that despite widespread use of azacitidine, there is a lack of improvement in long-term survival of patients with high-risk myelodysplastic syndromes. [35, 36]

A randomized controlled trial by Garcia-Manero et al compared rigosertib to the best supportive care in patients with myelodysplastic syndromes with excess blasts after failure of azacitidine or decitabine treatment. The study reported that rigosertib did not significantly improve overall survival compared with best supportive care. [37]


Growth Factor Therapy

The use of erythropoietin is helpful in patients who have low erythropoietin levels. Recent data from a phase III adult trial by the Eastern Cooperative group (ECOG) showed that erythropoietin treatment improved overall survival in patients responding to the erythropoiesis-stimulating agents compared with the best supportive care management. [38] This has also been confirmed by the Nordic and French MDS Study Groups.

Granulocyte colony-stimulating factor (G-CSF) has also been used, with a transient improvement in neutropenia.

Hesitation in using growth factors has been based on the known increased response of myelodysplastic clones to granulocyte-macrophage colony-stimulating factor (GM-CSF) and on reports that the use of G-CSF in children with severe aplastic anemia is associated with the later development of MDS or AML.